Abstract：
:The binding of carbamazepine and carbamazepine 10,11-epoxide to serum, albumin and alpha 1-acid glycoprotein (AAG) was determined and compared at drug concentrations ranging from 0.5 to 400 mg/l using equilibrium dialysis and liquid chromatography. The total binding of carbamazepine in serum was determined primarily by albumin and to a lesser extent (20-30%) by AAG. Modified Scatchard plots for carbamazepine binding in serum were biphasic, suggesting the presence of two binding sites on serum protein. Association constants characterizing the first (k1 = 2.4 X 10(4) l/mol) and second (k2 = 4.6 X 10(2) l/mol) binding sites agreed with those measured for AAG and albumin respectively. Modified Scatchard plots for carbamazepine 10,11-epoxide binding in serum were linear and serum binding was largely accounted for by binding to albumin. The epoxide metabolite did not bind to AAG. Carbamazepine binding to AAG was drug concentration-dependent over the concentration range considered to be therapeutic, while the percent binding values for carbamazepine and epoxide binding to albumin and serum from a normal individual were constant over this range. Computer simulations showed that physiological extremes in AAG and albumin concentrations can result in a range of carbamazepine unbound fractions of 0.17 to 0.47. These data suggest that normal variations in concentrations of both proteins may be the principal cause of interpatient variability in serum protein binding of carbamazepine.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
MacKichan JJ,Zola EMdoi
10.1111/j.1365-2125.1984.tb02496.xsubject
Has Abstractpub_date
1984-10-01 00:00:00pages
487-93issue
4eissn
0306-5251issn
1365-2125journal_volume
18pub_type
杂志文章abstract：:1. Determination of debrisoquine oxidation phenotype was carried out in 119 healthy subjects, 135 patients with chronic bronchitis and 153 patients with lung cancer, all of Caucasian origin. 2. A non-Gaussian distribution of the log D/HD ratio was observed in the three groups. 3. Assuming an antimode of 1.12, the prop...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1991.tb05575.x
更新日期：1991-05-01 00:00:00
abstract：:1 Apparent Vmax and Km for phenytoin were estimated in 40 children (aged 8--33 months) and 21 adults (aged 18--66 years). 2 The derived values of Vmax and Km were used to predict the plasma and salivary concentrations of phenytoin following a change in dose. There was a highly significant correlation between observed ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1981.tb01285.x
更新日期：1981-11-01 00:00:00
abstract：:The pharmacokinetics of single and co-administered didanosine and stavudine were evaluated in 10 HIV-seropositive subjects in an open, within subject design in which each subject received each of three treatments. Single doses of didanosine 100 mg were alternated randomly with single doses of stavudine 40 mg on days 1...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1994.tb04374.x
更新日期：1994-11-01 00:00:00
abstract：:1. N-hydroxylation is thought to be an essential step in the haemotoxicity of dapsone (DDS). To investigate both metabolism-dependent and cell-selective drug toxicity in vitro we have developed a three-compartment system in which an hepatic drug metabolizing system is contained within a central compartment separated b...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1993.tb05888.x
更新日期：1993-07-01 00:00:00
abstract：AIMS:To examine the influence of a pharmaceutical care programme on disease control and health-related quality of life in Type 2 diabetes patients in the United Arab Emirates. METHODS:A total of 240 Type 2 diabetes patients were recruited into a randomized, controlled, prospective clinical trial with a 12-month follow...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2009.03391.x
更新日期：2009-05-01 00:00:00
abstract：:For people seeking treatment, the course of heroin addiction tends to be chronic and relapsing, and longer duration of treatment is associated with better outcomes. Heroin addiction is strongly associated with deviant behaviour and crime, and the objectives in treating heroin addiction have been a blend of humane supp...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1111/bcp.12051
更新日期：2014-02-01 00:00:00
abstract：:1 A new osmotic pressure mediated delivery system for metoprolol (Lopresor Oros) has been evaluated by measuring the haemodynamic effects and pharmacokinetics after single and multiple oral dosing in young healthy volunteers. 2 Similar studies have been carried out in the same group using equivalent single and multipl...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1982.tb01391.x
更新日期：1982-03-01 00:00:00
abstract：AIMS:Dexloxiglumide is a new CCK(1) receptor antagonist under investigation for treatment of functional gastrointestinal disorders and is metabolized by CYP3A4 and CYP2C9. The objectives of these two separate randomized, two-period, two-treatment crossover studies were to investigate the effects of steady-state ketocon...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究,随机对照试验
doi：10.1111/j.1365-2125.2005.02465.x
更新日期：2005-11-01 00:00:00
abstract：AIMS:The aim of the present study was to investigate whether differences in total and peak drug exposure upon generic substitution are due to differences between formulations or to intrasubject pharmacokinetic variability of the active substance. METHODS:The study was designed as a retrospective reanalysis of existing...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.12828
更新日期：2016-04-01 00:00:00
abstract：AIMS:The pharmacokinetics of voriconazole show a nonlinear dose-exposure relationship caused by inhibition of its own CYP3A-dependent metabolism. Because the magnitude of autoinhibition also depends on voriconazole concentrations, infusion rate might modulate voriconazole exposure. The impact of four different infusion...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13297
更新日期：2017-09-01 00:00:00
abstract：:WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The population pharmacokinetics and limited sampling strategies for ciclosporin monitoring have been extensively studied in renal and liver transplant recipients. Little is known about the pharmacokinetics of ciclosporin in patients undergoing haematopoietic allogeneic stem c...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2011.04116.x
更新日期：2012-04-01 00:00:00
abstract：:1. Twenty-two patients with moderately severe essential hypertension were treated for a period of 12 months with guanfacine (BS 100-141), a new centrally-acting antihypertensive agent. A twice daily schedule was followed and the dose range of guanfacine was 1-8 mg daily. 2. In twenty patients satisfactory blood pressu...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1980.tb04906.x
更新日期：1980-01-01 00:00:00
abstract：AIMS:Hypertension is a common comorbidity of patients with COVID-19, SARS or HIV infection. Such patients are often concomitantly treated with antiviral and antihypertensive agents, including ritonavir and nifedipine. Since ritonavir is a strong inhibitor of CYP3A and nifedipine is mainly metabolized via CYP3A, the com...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14684
更新日期：2020-12-02 00:00:00
abstract：:1. The pharmacokinetics and pharmacodynamics of a single dose of trandolapril, an angiotensin converting enzyme (ACE) inhibitor with an active metabolite, trandolaprilat, which is in part further metabolised prior to renal elimination, were evaluated in 31 subjects with a wide range of renal function (creatinine clear...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：AIM:To evaluate the efficacy of scopolamine administered transdermally for the treatment of drooling in severely disabled patients. METHODS:A prospective, randomized, double-blind, crossover, placebo-controlled clinical trial was designed. The study group consisted of 30 handicapped patients with persistent drooling. ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1111/j.1365-2125.2010.03659.x
更新日期：2010-06-01 00:00:00
abstract：AIMS:Therapeutic drug monitoring of infliximab can guide clinical decisions in patients with loss of response and in those who can benefit from a de-intensification. The aim of this study was to determine the impact of therapeutic drug monitoring combined with Bayesian forecasting methodology on clinical response in a ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14410
更新日期：2020-06-03 00:00:00
abstract：WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT:Rosiglitazone is able to increase serum adiponectin levels significantly in Type 2 diabetic patients. :The role of genetic factors that determine the marked interindividual variability in glucose-lowering efficacy of rosiglitazone in Chinese patients is not known. The current st...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2008.03145.x
更新日期：2008-06-01 00:00:00
abstract：:Ten patients with mild to moderate hypertension were treated for 9 weeks with a tablet formulation of pinacidil. Mean supine blood pressure fell from 174/100 to 148/84 mm Hg and mean supine pulse increased by 3 beats/min. Daily dosage was 40-100 mg, given in two or three divided doses. Plasma urea increased significan...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.1984.tb02456.x
更新日期：1984-08-01 00:00:00
abstract：AIMS:To examine the hypothesis that sildenafil, a phosphodiesterase type 5 inhibitor that inhibits cGMP breakdown, could enhance nitric oxide-mediated vasodilation and reverse endothelial dysfunction in chronic smokers. METHODS:Flow-mediated dilation of the brachial artery and forearm postischemic reactive hyperemia (...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1046/j.1365-2125.2003.01974.x
更新日期：2004-02-01 00:00:00
abstract：:1. We investigated the effect of the haemostatic agent ethamsylate on aspirin-induced gastric mucosal bleeding. 2. Eighteen healthy subjects were studied three times: at the end of 48 h periods of treatment with (a) placebo, (b) aspirin 600 mg four times daily, (9 doses) and (c) aspirin 600 mg four times daily with ea...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1989.tb03512.x
更新日期：1989-07-01 00:00:00
abstract：AIMS:The aims of the present study were to describe the consumption trends of three groups of analgesics (non-opioids, and mild and strong opioids) between 2006 and 2015 in France, and compare this pattern of use with six European countries in 2015. METHODS:Annual drugs sales were extracted from the French national au...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.13564
更新日期：2018-06-01 00:00:00
abstract：:1. Medication errors are common in general practice and in hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. 2. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of e...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/j.1365-2125.2009.03425.x
更新日期：2009-06-01 00:00:00
abstract：:The current U.K. trial protocol (UKALL XI) for childhood lymphoblastic leukaemia demands mercaptopurine (MP) dose escalation in children who tolerate daily 75 mg/m2 MP (100% dose) without cytopenias. The previous trial (UKALL X) did not. MP metabolism was studied in a group of UKALL XI children (n = 21) who tolerated ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1046/j.1365-2125.1996.44921.x
更新日期：1996-10-01 00:00:00
abstract：:1 Twenty-four healthy male subjects had two consecutive drug nights at 2-week intervals using placebo and 80, 140 and 240 mg doses of phenobarbitone in a double-blind cross-over design. 2 Phenobarbitone produced significant dose-related decreases in sleep latency and number of awakenings, along with increased total sl...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1981.tb01218.x
更新日期：1981-09-01 00:00:00
abstract：AIMS:To determine whether enzyme-inducing antiseizure drugs (ASDs) affect the risk of developing chronic obstructive pulmonary disease (COPD) or lung cancer in smokers. METHODS:Cases of COPD and lung cancer and matched controls without these conditions were identified from a population of smokers with ≥1 prescription ...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1111/bcp.14501
更新日期：2020-08-01 00:00:00
abstract：:This double-blind study in 60 hospitalized female patients comparing midazolam 15 mg, oxazepam 15 mg and placebo, demonstrated an inter-group difference in favour of midazolam with regard to efficacy. The sleep parameters of onset latency and duration were improved by midazolam. All three compounds were very well tole...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1111/j.1365-2125.1983.tb02288.x
更新日期：1983-01-01 00:00:00
abstract：:1 Five normal subjects received pre-treatment with cimetidine 200 mg three times daily and 400 mg at night for 6 days, or matching placebo. 2 Caffeine (300 mg) was given orally before any treatment and at the beginning of the last day of each treatment course. Treatments were randomly allocated and separated by at lea...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1981.tb01194.x
更新日期：1981-08-01 00:00:00
abstract：AIM:Omalizumab, a humanized IgG monoclonal antibody that binds to human immunoglobulin E (IgE), interrupts the allergic cascade in asthmatic patients. The aim was to compare simultaneously drug exposure and IgE biomarker responses in Japanese and White patient populations. METHODS:An instantaneous equilibrium drug-lig...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1365-2125.2006.02803.x
更新日期：2007-05-01 00:00:00
abstract：AIMS:To facilitate and improve clinical research within Europe, the European Union (EU) adopted in 2001 the Clinical Trials Directive (EUCTD). The aim of this study was to compare duration between submission of a clinical drug trial application and approval by regulatory authorities in EU countries regulated by EUCTD v...
journal_title：British journal of clinical pharmacology
pub_type： 杂志文章,多中心研究
doi：10.1111/j.1365-2125.2008.03246.x
更新日期：2008-10-01 00:00:00
abstract：:A double-blind controlled study comparing the effects of intravenous Diazemuls (0.15 mg kg-1) with midazolam (0.07 mg kg-1) in patients with normal liver function and with cirrhosis and portal hypertension is described. The clinical effect of the two drugs was assessed by serial tests of psychomotor function before an...
journal_title：British journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1111/j.1365-2125.1986.tb02952.x
更新日期：1986-12-01 00:00:00
